1. Field of Invention
The present invention relates to cancer biology. More particularly, the present invention relates to a biomarker for gestational trophoblastic disease.
2. Description of Related Art
Gestational trophoblastic disease can be broadly divided into three groups: hydatidiform moles which represent abnormal placentas, tumor-like lesions and trophoblastic neoplasms. In recent years, progress has been made in elucidating the biology of human trophoblast, especially in identifying trophoblast-associated biomarkers. Characterization of these biomarkers has led to a further understanding of the lineage and differentiation program of trophoblast and various forms of trophoblastic tumors and tumor-like lesions. It is now clear that trophoblastic tumors and tumor-like lesions recapitulate the trophoblast present in the early developing placenta and implantation site.
Differentiation of trophoblastic tumors and tumor-like lesions from non-trophoblastic neoplasms can be difficult based on morphology alone. Although several trophoblastic biomarkers have been previously identified such as hPL, hCG, Mel-CAM (CD146), HLA-G, cytokeratin 18 and inhibin-α, there are several problems associated with their use.
First, most of the previously known trophoblast-associated biomarkers are not specific to trophoblastic lineage. For example, Mel-CAM and HLA-G can be expressed in certain normal adult tissues and several malignant neoplasms [Shih I M, Nesbit M, Herlyn M et al. A new Mel-CAM (CD146)-specific monoclonal antibody, MN-4, on paraffin-embedded tissue. Mod Pathol. 1998, 11:1098-106; Shih Ie M. Application of human leukocyte antigen-g expression in the diagnosis of human cancer. Hum Immunol. 2007, 68:272-6].
Second, most of the trophoblastic biomarkers reported so far are only expressed in certain subtypes of trophoblastic cells. For example, hPL and Mel-CAM are predominantly expressed in implantation site intermediate trophoblast and only very focally in chorionic-type intermediate trophoblastic cells. Thus, hPL and Mel-CAM serve as biomarkers for placental site trophoblastic tumor (PSTT) but not for epitheloid trophoblastic tumor (ETT) and placental site nodules (PSN) which are related to chorionic-type intermediate trophoblastic cells. Similarly, p63 immunoreactivity can only be detected in chorionic-type intermediate trophoblastic cells and the related lesions including ETT and PSN but not in PSTT.
Third, antibodies that react specifically to some of the trophoblast-associated biomarkers on paraffin sections are not currently available from commercial sources. For example, commercially available antibodies to HLA-G and anti-Mel-CAM not as specific and sensitive when used on paraffin sections as compared to 4H84 monoclonal antibody [McMaster M T, Librach C L, Zhou Y et al. Human placental HLA-G expression is restricted to differentiated cytotrophoblasts. J. Immunol. 1995, 154:3771-8.; Singer G, Kurman R J, McMaster M et al. HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis. Am J Surg Pathol. 2002, 26 (7):914-20] and MN-4 monoclonal antibody [Shih I M, Nesbit M, Herlyn M et al. A new Mel-CAM (CD146)-specific monoclonal antibody, MN-4, on paraffin-embedded tissue. Mod Pathol. 1998, 11:1098-106] that recognize HLA-G and Mel-CAM epitope, respectively. Both 4H84 and MN-4 antibodies have been well characterized and extensively used for research purposes but they are not yet commercially available.